Defining the Molecular Character of the Developing and Adult Kidney Podocyte

BackgroundThe podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. Methodology/Principal FindingsIn this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. Conclusions/SignificanceThe complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells.背景 足细胞（podocyte）是一类特殊的细胞类型，包裹着肾肾小球的毛细血管。尽管其起源于中胚层，但可伸出类似轴突的突起缠绕于毛细血管表面。此类突起可进一步分化为更纤细的足突（foot processes），足突之间相互交错镶嵌，间隙中形成裂孔膜（slit diaphragm），肾小球滤液必须经此结构完成滤过。足细胞因其在肾脏发育与疾病发生中的关键作用，一直是科研领域的关注热点。 方法学与主要发现 本研究鉴定并表征了一种新型转基因小鼠品系MafB-GFP，该品系可在发育早期特异性标记肾脏足细胞。随后利用该小鼠模型，通过荧光激活细胞分选技术，从胚胎发育第13.5天（E13.5）、第15.5天（E15.5）的胚胎以及成年小鼠体内纯化得到足细胞。继而采用基因芯片技术，在全基因组层面解析不同发育阶段足细胞的基因表达状态。研究得到了清晰的分子特征图谱，明确了多组可赋予足细胞神经元、肌肉及吞噬细胞特性的基因。本研究还解析了调控足细胞命运的完整转录因子组合调控代码，并明确了足细胞所表达的生长因子与受体的全基因组列表。 结论与意义 本研究首次明确了体内足细胞的完整分子特征。其活跃的分子功能与生物学过程进一步阐明了足细胞独特的特征组合。本研究构建了发育中及成年小鼠肾脏足细胞的基因表达图谱资源库，将为后续针对这类特殊细胞的相关研究提供重要指导。